PARACEST agents

PARACEST agents are particularly well adapted for the development of responsive probes, since the rate of exchange and the chemical shift of the protons leading to a PARACEST effect depend on various physico-chemical parameters. We will discuss several examples from this field in the following section on Responsive Imaging Probes. ... 

For Gdin-based agents, the relaxivity response is most often related to a change in water accessibility or to the variation of the size and consequently of the rotational correlation time of the complex. In addition to Gdm complexes, PARACEST agents are... 

PARACEST agents with a response to enzymatic activity have also been reported. Pagel et al. used a Tm1 DOTA monoamide complex containing a peptide chain which is hydrolyzed by the Caspase-3 enzyme (204,205). Following enzymatic cleavage, the PARACEST effect originating from the amide proton disappears due to the hydrolysis of the amide bond. 

The saturation transfer is induced by the selective irradiation of the mobile protons of the probe with a proper radiofrequency field. When different pools of exchangeable protons are available, this modality enables the set-up of ratiometric methods in which a responsive PARACEST agent provides a MRI response no longer dependent on its absolute concentration (119-120). 

Zhang, S., Merritt, M., Woessner, D.E., etal. (2003) PARACEST agents modulating MRl contrast via water proton exchange. Accounts of Chemical Research, 36, 783—790. 

Although PARACEST agents are very good pH reporters due to their nature (modulation of the proton exchange rate via the pH of the solution), " " most often their pH-dependent behavior does not involve supramolecular interactions. Consequently, they are not discussed here. 

Zhang S, Merritt M, Woessner BE, Lenkinski RE, Sherry AB. PARACEST agents modulating MRI contrast via water proton exchange. Acc Chem Res 2003 36 783-790. 

Comparison of the sensitivity limits of rdaxation agents verms PARACEST agents with optimal water exchange... 

The modified Bloch equations firr two site exchange predict a sinqile relationship between net magnetization of bulk water and cotKxntiation of PARACEST agent (equation 1). ... 

Figjure 3. Plot of the Jhactional decrease in bulk water signal intensity expected for a PARACEST agent having a bound water lifetime of3ps... 

Huang C-H, Hammell J, Ratnakar SJ, Sherry AD, Morrow JR. Activation of a PARACEST agent for MRI through selective outersphere interactions with phosphate diesters. Inorg Chem. 2010 49(13) 5963-5970. 

Huang C-H, Morrow JR. A PARACEST agent responsive to inner- and outer-sphere phosphate ester interactions for MRI applications. J Am Chem Soc. 2009 131(12) 4206 207. 

---